Although tobacco use is generally associated with detrimental health related effects including respiratory disease, cardiovascular disease and cancer, the results from a large series of studies done between 1961 and 2000 show that there is about a 50% decrease in the incidence of Parkinson’s disease in tobacco users. Parkinson’s disease is a relatively common movement disorder which occurs in approximately 1% of the population over 50 years of age and is due to degeneration of dopamine nerve cells in the brain. Treatments available to date involve administration of the dopamine drug L-dopa and/or other drugs which stimulate the dopamine system in the brain. Although quite beneficial in the early stages of the disease, these drugs become less effective with continued treatment. Disease progression is inevitable with immobility and dementia present at the end stages. The development of new approaches is thus essential for Parkinson’s disease management. Our rationale for investigating a role for nicotine stems from recent studies which show that nicotine drug therapy, in combination with l-dopa, may be beneficial in relieving some of the motor and memory difficulties that occur after nigrostriatal degeneration, and furthermore from experimental evidence which shows that nicotine may exert long term protection against nerve cell damage.

The goal of our research is to study nicotinic receptors in brain tissue in an animal model of Parkinson’s disease. Nicotinic receptors are the molecules in the brain that are activated by nicotine. Experimental studies have shown that nicotinic receptors are decreased in some brain areas in Parkinson’s disease. The fact that receptors are decreased in this neurological disorder could suggest that stimulation of the receptors which remain may result in a return of functions somewhat closer to normal. However, when nicotine enters the body either through smoking, or use of the nicotine patch or gum, it stimulates many different types of nicotinic receptor both in the brain and in the rest of the body. Nicotine treatment may therefore result in numerous biological effects in the body, only some of which are desirable or beneficial. For this reason it is important to identify which nicotinic receptors are changed in Parkinson’s disease. Once this is known, it may be possible to develop drugs which act with the receptors that are deficient in Parkinson’s disease, and thus optimize beneficial and minimize negative side effects. To study the receptors that are changed in Parkinson’s disease brain, we will use a number of different experimental techniques and approaches involving drugs and reagents which target nicotinic receptors in different ways. This work may lead to the development of new therapies for the treatment of Parkinson’s disease.